Zogenix Reports Positive Results from Phase III Trial of Rare Childhood Epilepsy Study

 

Emeryville, California-based Zogenix announced positive topline data from its Phase III trial of Fintepla (fenfluramine) in Lennox-Gastaut Syndrome (LGS). LGS is a rare form of childhood-onset epilepsy marked by many different types of seizures. They don’t often respond to currently available seizure drugs.

The global Phase III trial was split into two parts. The first was a double-blind, placebo-controlled study evaluating the safety, tolerability and efficacy of Fintepla when added to a patient’s regular anti-epileptic treatment. Part 1 included a total of 263 patients between the ages of 2 and 35 years whose seizures were uncontrolled. They were split into three treatment groups receiving one of two doses of Fintepla or a placebo. Part 2 of the trial is an ongoing 12-month open-label extension study evaluating long-term safety, tolerability and effectiveness of the drug.

The trial met its primary endpoint, showing a highly statistically significant decrease from baseline compared to placebo in the median percent change in monthly drop seizure frequency. Patients receiving 0.7 mg/kg/day of Fintepla had a median decrease of 26.5% compared to 7.8% in the placebo group. Patients receiving the lower dose, 0.2 mg/kg/day, was 13.2%, which did not hit statistical significance compared to placebo.

The drug was generally well-tolerated and consistent with those reported in two previous Phase III trials in Dravet syndrome.

“LGS is a rare and severe form of epilepsy where nearly all patients have highly treatment resistant and lifelong seizures,” said Kelly Knupp, associate professor at Children’s Hospital Colorado and principal investigator of the trial. “As a result, the frequent falls and injuries, and also the cognitive impairment, limit the quality of life for patients and caregivers, even with current treatment options.”

Knupp added, “The results observed in this placebo-controlled study are indicative of the potential of fenfluramine to treat patients with refractory LGS. If approved, Fintepla could represent an important new treatment option for these patients and their families in need.”

The drug previously received Orphan Drug designation for LGS by the U.S. Food and Drug Administration (FDA) and the European Commission (EC). Currently, Zogenix’ New Drug Application (NDA) is under Priority Review by the FDA for seizures associated with Dravet syndrome. It has a target action date of March 25, 2020.

It is also under review for Dravet syndrome by the European Medicines Agency (EMA). Both the NDA and EMA’s Marketing Authorization Application (MAA) are based on results from two pivotal Phase III trials and an interim analysis from an ongoing open-label extension study. The drug is also being developed in Japan.

In April 2019, the FDA issued a Refuse to File (RTF) letter to the company for its NDA for Fintepla for Dravet syndrome. Zogenix indicated at the time the FDA had concerns over non-clinical studies that were not submitted over chronic administration of the drug and what Zongenix said was an incorrect version of a clinical dataset. It then resubmitted the NDA, which was accepted for review.

At the same time, although separate, the FDA rescinded its Breakthrough Therapy Designation for the drug for seizures associated with Dravet syndrome, noting the decision is because there are now two approved drugs for the disease, so the criteria for Breakthrough Therapy Designation had already been met. Those drugs are UK-based GW Pharmaceuticals’ Epidiolex (cannabidiol) and Diacomit (stiripentol), developed by Laboratoires Biocodex, headquartered in Gentilly, France.